Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Psychiatry
Published in: BMC Psychiatry 1/2014

Open Access 01-12-2014 | Research article

Body mass index and metabolic parameters in patients with schizophrenia during long-term treatment with paliperidone palmitate

Authors: Jennifer Kern Sliwa, Dong-Jing Fu, Cynthia A Bossie, Ibrahim Turkoz, Larry Alphs

Published in: BMC Psychiatry | Issue 1/2014

Login to get access

Abstract

Background

There is a strong association between weight gain and metabolic events in patients with schizophrenia receiving many of the second-generation antipsychotic agents. We explored the relationship between body mass index (BMI) and metabolic events in patients with schizophrenia receiving long-acting injectable paliperidone palmitate (PP) in a long-term trial.

Methods

We conducted a post hoc analysis of data from a PP study that included a 33-week open-label transition (TR) and maintenance phase; a variable duration, randomized, double-blind (DB), placebo-controlled phase and a 52-week open-label extension (OLE) phase. Overall, 644 patients received PP continuously from study entry through discontinuation or study completion and were grouped by baseline BMI (kg/m2): underweight (BMI <19; n = 29, 4.5%), normal-weight (BMI 19- < 25; n = 229, 35.6%), overweight (BMI 25- < 30; n = 232, 36.0%) and obese (BMI ≥30; n = 154, 23.9%). Metabolic treatment-emergent adverse events (TEAEs) and changes in related laboratory results from TR baseline were analyzed.

Results

PP exposure was similar across BMI groups; overall mean (SD) dose/month was 70.3 (17.17) mg eq. [109.6 (26.78) mg]; median duration of exposure was 204 days (6 to 1009 days). Occurrences of metabolic TEAEs overall by group were 0% (underweight), 14.9% (normal-weight), 14.7% (overweight), and 24.0% (obese). The most common (≥2%) metabolic TEAE were weight gain and elevated blood levels of glucose, lipids, and insulin. Mean BMI and weight increased in normal-weight and overweight groups at DB endpoint, and in underweight, normal-weight and overweight groups at OLE endpoint (p ≤0.05). No consistent trend for increased metabolic-related laboratory values by baseline BMI group was observed. Homeostatic model assessments for insulin resistance indicated preexisting insulin resistance at baseline, with minimal changes at OLE endpoint across baseline BMI groups.

Conclusion

Occurrences of metabolic-related TEAEs trended with greater BMI status in patients with schizophrenia treated with PP; consistent trends in metabolic-related laboratory values were not observed.

Trial registration

This study is registered at ClinicalTrials.gov (NCT00518323).
Appendix
Available only for authorised users
Literature
1.
Schultz SH, North SW, Shields CG: Schizophrenia: a review. Am Fam Physician. 2007, 75 (12): 1821-1829.PubMed
2.
Balf G, Stewart TD, Whitehead R, Baker RA: Metabolic adverse events in patients with mental illness treated with antipsychotics: a primary care perspective. Prim Care Companion J Clin Psychiatry. 2008, 10 (1): 15-24. 10.4088/PCC.v10n0104.CrossRefPubMedPubMedCentral
3.
McIntyre RS, McCann SM, Kennedy SH: Antipsychotic metabolic effects: weight gain, diabetes mellitus, and lipid abnormalities. Can J Psychiatry. 2001, 46 (3): 273-281.PubMed
4.
Croarkin PE, Jacobs KM, Bain BK: Diabetic ketoacidosis associated with risperidone treatment?. Psychosomatics. 2000, 41 (4): 369-370. 10.1176/appi.psy.41.4.369.CrossRefPubMed
5.
Hedenmalm K, Hagg S, Stahl M, Mortimer O, Spigset O: Glucose intolerance with atypical antipsychotics. Drug Saf. 2002, 25 (15): 1107-1116. 10.2165/00002018-200225150-00005.CrossRefPubMed
6.
Lindenmayer JP, Czobor P, Volavka J, Citrome L, Sheitman B, McEvoy JP, Cooper TB, Chakos M, Lieberman JA: Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psychiatry. 2003, 160 (2): 290-296. 10.1176/appi.ajp.160.2.290.CrossRefPubMed
7.
McEvoy JP, Meyer JM, Goff DC, Nasrallah HA, Davis SM, Sullivan L, Meltzer HY, Hsiao J, Scott Stroup T, Lieberman JA: Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the clinical antipsychotic trials of intervention effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res. 2005, 80 (1): 19-32. 10.1016/j.schres.2005.07.014.CrossRefPubMed
8.
Falissard B, Mauri M, Shaw K, Wetterling T, Doble A, Giudicelli A, De Hert M: The METEOR study: frequency of metabolic disorders in patients with schizophrenia. Focus on first and second generation and level of risk of antipsychotic drugs. Int Clin Psychopharmacol. 2011, 26 (6): 291-302. 10.1097/YIC.0b013e32834a5bf6.CrossRefPubMed
9.
Tschoner A, Engl J, Laimer M, Kaser S, Rettenbacher M, Fleischhacker WW, Patsch JR, Ebenbichler CF: Metabolic side effects of antipsychotic medication. Int J Clin Pract. 2007, 61 (8): 1356-1370. 10.1111/j.1742-1241.2007.01416.x.CrossRefPubMed
10.
Lean ME, Pajonk FG: Patients on atypical antipsychotic drugs: another high-risk group for type 2 diabetes. Diabetes Care. 2003, 26 (5): 1597-1605. 10.2337/diacare.26.5.1597.CrossRefPubMed
11.
Marder SR, Essock SM, Miller AL, Buchanan RW, Casey DE, Davis JM, Kane JM, Lieberman JA, Schooler NR, Covell N, Stroup S, Weissman EM, Wirshing DA, Hall CS, Pogach L, Pi-Sunyer X, Bigger JT, Friedman A, Kleinberg D, Yevich SJ, Davis B, Shon S: Physical health monitoring of patients with schizophrenia. Am J Psychiatry. 2004, 161 (8): 1334-1349. 10.1176/appi.ajp.161.8.1334.CrossRefPubMed
12.
American Diabetes Association: Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004, 27 (2): 596-601.CrossRef
13.
14.
Hough D, Gopal S, Vijapurkar U, Lim P, Morozova M, Eerdekens M: Paliperidone palmitate maintenance treatment in delaying the time-to-relapse in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. Schizophr Res. 2010, 116 (2–3): 107-117.CrossRefPubMed
15.
Gopal S, Vijapurkar U, Lim P, Morozova M, Eerdekens M, Hough D: A 52-week open-label study of the safety and tolerability of paliperidone palmitate in patients with schizophrenia. J Psychopharmacol. 2010, 25 (5): 685-697.CrossRefPubMed
16.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985, 28 (7): 412-419. 10.1007/BF00280883.CrossRefPubMed
17.
Wallace TM, Levy JC, Matthews DR: Use and abuse of HOMA modeling. Diabetes Care. 2004, 27 (6): 1487-1495. 10.2337/diacare.27.6.1487.CrossRefPubMed
18.
Kagal UA, Torgal SS, Patil NM, Malleshappa A: Prevalence of the metabolic syndrome in schizophrenic patients receiving second-generation antipsychotic agents--a cross-sectional study. J Pharm Pract. 2012, 25 (3): 368-373. 10.1177/0897190012442220. Epub 2012CrossRefPubMed
19.
Pramyothin P, Khaodhiar L: Metabolic syndrome with the atypical antipsychotics. Curr Opin Endocrinol Diabetes Obes. 2010, 17 (5): 460-466. 10.1097/MED.0b013e32833de61c.CrossRefPubMed
20.
Olfson M, Marcus SC, Corey-Lisle P, Tuomari AV, Hines P, L’Italien GJ: Hyperlipidemia following treatment with antipsychotic medications. Am J Psychiatry. 2006, 163 (10): 1821-1825. 10.1176/appi.ajp.163.10.1821.CrossRefPubMed
21.
McEvoy JP, Lieberman JA, Perkins DO, Hamer RM, Gu H, Lazarus A, Sweitzer D, Olexy C, Weiden P, Strakowski SD: Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison. Am J Psychiatry. 2007, 164 (7): 1050-1060. 10.1176/appi.ajp.164.7.1050.CrossRefPubMed
22.
Gopal S, Hough DW, Xu H, Lull JM, Gassmann-Mayer C, Remmerie BM, Eerdekens MH, Brown DW: Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized, double-blind, placebo-controlled, dose–response study. Int Clin Psychopharmacol. 2010, 25 (5): 247-256. 10.1097/YIC.0b013e32833948fa.CrossRefPubMed
23.
Kramer M, Litman R, Hough D, Lane R, Lim P, Liu Y, Eerdekens M: Paliperidone palmitate, a potential long-acting treatment for patients with schizophrenia. Results of a randomized, double-blind, placebo-controlled efficacy and safety study. Int J Neuropsychopharmacol. 2010, 13 (5): 635-647. 10.1017/S1461145709990988.CrossRefPubMed
24.
Nasrallah HA, Gopal S, Gassmann-Mayer C, Quiroz JA, Lim P, Eerdekens M, Yuen E, Hough D: A controlled, evidence-based trial of paliperidone palmitate, a long-acting injectable antipsychotic, in schizophrenia. Neuropsychopharmacology. 2010, 35 (10): 2072-2082. 10.1038/npp.2010.79.CrossRefPubMedPubMedCentral
25.
Pandina GJ, Lindenmayer JP, Lull J, Lim P, Gopal S, Herben V, Kusumakar V, Yuen E, Palumbo J: A randomized, placebo-controlled study to assess the efficacy and safety of 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia. J Clin Psychopharmacol. 2010, 30 (3): 235-244. 10.1097/JCP.0b013e3181dd3103.CrossRefPubMed
26.
27.
Allison DB, Casey DE: Antipsychotic-induced weight gain: a review of the literature. J Clin Psychiatry. 2001, 62 (Suppl 7): 22-31.PubMed
28.
Emsley R, Oosthuizen P, Koen L, Niehaus DJ, Medori R, Rabinowitz J: Oral versus injectable antipsychotic treatment in early psychosis: post hoc comparison of two studies. Clin Ther. 2008, 30 (12): 2378-2386. 10.1016/j.clinthera.2008.12.020.CrossRefPubMed
29.
Markowitz M, Fu DJ, Levitan B, Gopal S, Turkoz I, Alphs L: Long-acting injectable paliperidone palmitate versus oral paliperidone extended release: a comparative analysis from two placebo-controlled relapse prevention studies. Ann Gen Psychiatry. 2013, 12 (1): 22-10.1186/1744-859X-12-22.CrossRefPubMedPubMedCentral
30.
Coppola D, Liu Y, Gopal S, Remmerie B, Samtani MN, Hough DW, Nuamah I, Sulaiman A, Pandina G: A one-year prospective study of the safety, tolerability and pharmacokinetics of the highest available dose of paliperidone palmitate in patients with schizophrenia. BMC Psychiatry. 2012, 12: 26-10.1186/1471-244X-12-26. doi:10.1186/1471-1244X-1112-1126CrossRefPubMedPubMedCentral
Metadata
Title
Body mass index and metabolic parameters in patients with schizophrenia during long-term treatment with paliperidone palmitate
Authors
Jennifer Kern Sliwa
Dong-Jing Fu
Cynthia A Bossie
Ibrahim Turkoz
Larry Alphs
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2014
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/1471-244X-14-52

Other articles of this Issue 1/2014

BMC Psychiatry 1/2014 Go to the issue

Research article

Alterations of regional homogeneity in pediatric bipolar depression: a resting-state fMRI study

Study protocol

Reducing the duration of untreated psychosis and its impact in the U.S.: the STEP-ED study

Research article

Effects of mental health self-efficacy on outcomes of a mobile phone and web intervention for mild-to-moderate depression, anxiety and stress: secondary analysis of a randomised controlled trial

Erratum

Erratum to: A randomized, double-blind, placebo-controlled study of rapid-acting intramuscular olanzapine in Japanese patients for schizophrenia with acute agitation

Research article

A systematic review and meta-analysis of randomised controlled trials of peer support for people with severe mental illness

Research article

Verification of the utility of the social responsiveness scale for adults in non-clinical and clinical adult populations in Japan